title: Clinical significance of VEGFR-2 and ¹⁸F-FDG PET/CT SUVmax pretreatment score in predicting the long-term outcome of patients with locally advanced rectal cancer treated with neoadjuvant therapy.
abstract: OBJECTIVE
  Vascular endothelial growth factor receptor-2 (VEGFR-2), epidermal growth factor receptor-1 (EGFR), and cyclooxygenase-2 (COX-2) stimulate key processes involved in tumor progression and are important targets for cancer drugs. (18)F-FDG maximum standardized uptake value (SUVmax) is a marker of tumor metabolic activity. The purpose of this study was to measure SUVmax combined with VEGFR-2, EGFR and COX-2 proteins in pretreatment tumor biopsies from patients with locally advanced rectal cancer receiving intensive neoadjuvant treatment and to correlate the findings with clinical outcome.
  
  
  METHODS
  VEGFR-2, EGFR and COX-2 were measured using the immunoreactive score (IRS). SUVmax (median 8.4) was quantified in tumors with molecular overexpression (IRS ≥3 + SUVmax ≥ 8.4 indicating active tumors; SUVmax <8.4 indicating inactive tumors). The Cox proportional hazards model was used to explore associations between tumor markers, disease-free survival (DFS) and overall survival (OS).
  
  
  RESULTS
  The study group comprised 38 patients with a median follow-up of 69.3 months (range 4.5 - 92 months). Multivariate analysis showed that active tumors (overexpressing VEGFR-2, high SUVmax) were associated with worse DFS (HR 4.73, 95 % CI 1.18 - 22.17; p = 0.04) and OS (HR 4.28, 95 % CI 1.04 - 20.12; p = 0.05).
  
  
  CONCLUSIONS
  Active tumors overexpressing VEGFR-2 are associated with a worse overall outcome in patients with rectal cancer treated with induction chemotherapy followed by pelvic chemoradiation and surgery. The optimal diagnostic cut-off level for this novel biomarker association should be investigated. Evaluation in a clinical trial is required to determine whether selected patients could benefit from a VEGFR-targeting drug.
authors.affiliation: Department of Oncology, Hospital General Universitario Gregorio Marañón, Madrid, Spain, cvsole@uc.cl.
authors.forename: Claudio V
authors.initials: CV
authors.lastname: Sole
authors.forename: Felipe A
authors.initials: FA
authors.lastname: Calvo
authors.forename: Emilio
authors.initials: E
authors.lastname: Alvarez
authors.forename: Isabel
authors.initials: I
authors.lastname: Peligros
authors.forename: Pilar
authors.initials: P
authors.lastname: Garcia-Alfonso
authors.forename: Carlos
authors.initials: C
authors.lastname: Ferrer
authors.forename: Enrique
authors.initials: E
authors.lastname: Ochoa
authors.forename: Rafael
authors.initials: R
authors.lastname: Herranz
authors.forename: Jose L
authors.initials: JL
authors.lastname: Carreras
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000628:therapy; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D059186:Chemoradiotherapy, Adjuvant; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D064847:Multimodal Imaging; D020360:Neoadjuvant Therapy; D049268:Positron-Emission Tomography; D011237:Predictive Value of Tests; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D012004:Rectal Neoplasms / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000628:therapy; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D051546:Cyclooxygenase 2; C512478:EGFR protein, human; D066246:ErbB Receptors; D040301:Vascular Endothelial Growth Factor Receptor-2